2-Oxoglutarate Dehydrogenase

Introduction
The enzyme 2-Oxoglutarate Dehydrogenase E1o is a subunit the 2-Oxoglutarate Dehydrogenase multi enzyme complex. This subunit is a homo-dimer and one of three enzymes that make up the multi-enzyme complex of 2-Oxoglutarate Dehydrogenase. Each of the monomers that make up the homo-dimer have an adenosine monophosphate cofactor that facilitates the catalysis. E1o is not categorized in the Structural Classification of Proteins (SCOP); however, the secondary structure of one of the dimers shows that this enzyme has large sections of alpha-helices followed by a large sections of parallel beta-pleated sheets these alpha and beta subunits are fused as a single polypeptide.

Catalysis
E1o catalyzes the oxidative decarboxylation of alpha-ketoglutarate to Succinyl-CoA at its active site in the fourth step of the metabolic citric acid cycle by acting as a base to facilitate the decarboxylation. The main residues responsible for the catalysis are thought to be His 260, Phe 227, Gln685, His 729, Ser302, and His 298. E1o is also thought to have a single active site. E1o also requrires two cofactors in order for it to function properly, Thiamine diphosphate and divalent magnesium ion if either are not present then the enzyme has nearly no activity. The specific mexhanism of the E1o subunit are currently unknown; however, There are several theories as to how it functions, among them is the Hexa Uni Ping Pong theory. Even though the mechanism isn't fully know the kinetic data have be calculated and are as follows:
 * KM: 0.14 ± 0.04 mM
 * Vmax : 9 ± 3 μmol.min-1.mg-1

Regulation
E1o catalyzes a rate limiting step in the Kreb's Cycle and lies far form equilibrium (ΔG= -33kJ/mol). As it is a limiting step this makes it a useful reaction to regulate in order to control the Kreb's Cycle. E1o is inhibited by both NADH and Succinyl-CoA via non competitive feedback inhibition.

Transfer to E2o
The overall complex (all of the sub units) help catalysis by keeping the necessary substrates for the reaction close within the enzyme so that it is more likely that the substrate will be in favorable conformation. This enzyme is also part of a larger multienzyme complex that channels the intermediates in the catalysis between subunits of the complex thus minimizing unwanted side reactions. Not only do the subunits ferry products back and forth but each of the mers in the E1o homodimer are connected via a cavity lined with acidic residues thus increasing the dimer's ability to act as a base.

3D structures of 2-Oxoglutarate dehydrogenase
2cyu – Ec2OD E3-binding domain – Escherichia coli – NMR

2jgd - Ec2OD E1

3ery – 2OD E1 peptide + H-2 class I histocompatibility antigen – human

2eq7 – Tt2OD E3+E2 – Thermus thermophilus

2yqu - Tt2OD E3